Unclassifiable lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma is a new category of B-cell lymphoma appearing in the new World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements. According to the presence of two or three rearrangements, these lymphomas are called double-hit lymphomas or triple-hit lymphomas (THL), respectively. Here we report two cases of THL with MYC, BCL2, and BCL6 rearrangements and t(3;8)(q27;q24) diagnosed in one center in the last two years.
"Recently, a new subset of lymphoma, one with concurrent BCL2 and MYC translocations, has received great attention. It has been proposed that this unclassifiable entity could be called ''doublehit'' or ''triple-hit'' lymphoma depending on the number of aberrations present, such as MYC translocation in the setting of a complex karyotype with the addition of rearrangements in BCL2 and, less commonly, BCL6 . DHL has the double disadvantage of MYC (proliferation) and BCL2 (anti-apoptosis) . "
[Show abstract][Hide abstract] ABSTRACT: Double-hit or triple-hit B-cell lymphomas (DHL and THL) are rare subtype lymphomas usually associated with poor prognosis. It is defined by two or three recurrent chromosome translocations; MYC/8q24 loci, usually in combination with the t (14; 18) (q32; q21) bcl-2 gene or/and BCL6/3q27 chromosomal translocation. DHL was often observed both in de-novo diffuse large B cell lymphomas (DLBCL). It is otherwise unclassifiable, showing features intermediate that of large B-cell lymphoma and Burkitt lymphoma. Here, we present two follicular lymphoma patients; one transformed to THL, another transformed to DHL. Both cases revealed aggressive clinical courses with poor prognosis and associated with acquisition of c-Myc gene (MYC) and central nervous system (CNS) involvement. We reviewed the related literature, correlated the immunophenotype and clinical manifestations such as response to therapy and prognosis. Although the incidence of DHT and THL is low, cytogenetic and FISH analyses should be included when B-cell lymphoma patients experience relapse or refractory course of disease. We concluded that c-Myc may contribute to aggressive transformation, and more mechanism-based therapy should be explored.
International journal of clinical and experimental pathology 04/2013; 6(4):788-94. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Follicular lymphoma (FL) in situ (FLIS) was first described and proposed as a distinct entity associated with an indolent clinical course in 2002. To gain further insight into the biology of this enigmatic lymphoproliferation, we analyzed morphologic, phenotypic, cytogenetic and molecular features of tissue specimens manifesting a pattern of follicular colonization by Bcl-2(bright+)CD10(+) B-cells and associated lymphomas from 13 adults and evaluated their clinical outcomes. We observed this immunoarchitectural pattern in lymph nodes (n = 9), at extranodal sites (n = 5), or at both locations (n = 1) at diagnosis. All except 3 cases showed concomitant bright CD10 expression. Six (46%) patients had synchronous and 2 (15%) developed metachronous B-cell lymphomas, with 5 representing high-grade lymphomas. The Bcl-2(bright+)CD10(+) B-cells colonizing reactive follicles and synchronous lymphomas were clonally related in 4/5 (80%) cases analyzed and 5/6 (83%) displayed BCL2 translocations. Two cases exhibited complex karyotypes in both components; a genetic "triple hit" was detected in one instance and 2 copies of t(14,18) were observed in a lymph node biopsy lacking evidence of lymphoma from an individual with stage 4 disease, suspected on imaging, who subsequently displayed a mantle zone/perifollicular infiltrate of Bcl-2(bright+)CD10(+) B-cells in the adenoids. Our findings suggest that bright Bcl-2, and often bright CD10 expression, by B-cells colonizing reactive follicles might represent a phenomenon related to follicular homing of lymphoma, rather than being an attribute of preneoplastic FL precursors. Furthermore, due to the relatively high frequency of overt lymphomas observed, complete staging workup is recommended for patients exhibiting a Bcl-2(bright+)CD10(+) B-cell follicular colonization pattern on biopsy.
Human pathology 01/2013; 44(7). DOI:10.1016/j.humpath.2012.10.022 · 2.77 Impact Factor
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